Hmo1: A versatile member of the high mobility group box family of chromosomal architecture proteins

Abstract

Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures, which is facilitated by linker histone H1. Formation of chromatin compacts and protects the genome, but also hinders DNA transactions. Cells have evolved mechanisms to modify/remodel chromatin resulting in chromatin states suitable for genome functions. The high mobility group box (HMGB) proteins are non-histone chromatin architectural factors characterized by one or more HMGB motifs that bind DNA in a sequence nonspecific fashion. They play a major role in chromatin dynamics. The Saccharomyces cerevisiae (yeast hereafter) HMGB protein Hmo1 contains two HMGB motifs. However, unlike a canonical HMGB protein that has an acidic C-terminus, Hmo1 ends with a lysine rich, basic, C-terminus, resembling linker histone H1. Hmo1 exhibits characteristics of both HMGB proteins and linker histones in its multiple functions. For instance, Hmo1 promotes transcription by RNA polymerases I and II like canonical HMGB proteins but makes chromatin more compact/stable like linker histones. Recent studies have demonstrated that Hmo1 destabilizes/disrupts nucleosome similarly as other HMGB proteins in vitro and acts to maintain a common topological architecture of genes in yeast genome. This minireview reviews the functions of Hmo1 and the underlying mechanisms, highlighting recent discoveries.

Keywords: Hmo1; High mobility group box proteins; Chromatin; Chromatin remodeling; Gene regulation; Ribosomal DNA; Ribosomal protein genes; DNA damage response; Linker histone

Core Tip: The evolutionarily conserved high mobility group box (HMGB) family proteins are major non-histone chromosomal architectural factors characterized by one or more HMGB motifs that bind DNA in a sequence nonspecific fashion. They play a major role in chromatin dynamics that impact various cellular functions. The Saccharomyces cerevisiae (yeast hereafter) HMGB protein Hmo1 contains two HMGB motifs. Hmo1 functions in multiple cellular processes including genome maintenance, chromatin dynamics, gene transcription, and DNA damage response. However, the underlying mechanisms have only been partially elucidated. Moreover, to what extent Hmo1 functionally resembles its mammalian counterparts has not been fully addressed. Recent studies revealed that Hmo1 binds and destabilizes/disrupts nucleosome similarly as well-characterized human HMGB proteins and that Hmo1 plays a role in maintaining a topological architecture of genes in the yeast genome.